Practical synthesis of aryl-2-methyl-3-butyn-2-ols from aryl bromides via conventional and decarboxylative copper-free Sonogashira coupling reactions

• Andrea Caporale,
• Stefano Tartaggia,
• Andrea Castellin and
• Ottorino De Lucchi

Beilstein J. Org. Chem. 2014, 10, 384–393, doi:10.3762/bjoc.10.36

• obtained in a one-pot protocol with a considerable reduction of synthetic and purification steps with respect to traditional procedures [51][52][62]. Instead, when looking to the preparation of terminal alkynes from propiolic acid derivatives, the Cu-catalyzed protodecarboxylation of alkynoic acids [67][68

• pharmaceutical intermediate [71] and a promising anti-Alzheimer [72], we found that the Pd/Cu-catalyzed Sonogashira coupling reaction of 3-bromoaniline (1a) with 4 is the actual industrial process for the synthesis of 2a in high yield [73][74][75] (Scheme 1). However, when the reaction is performed at industrial

3-Pyridinols and 5-pyrimidinols: Tailor-made for use in synergistic radical-trapping co-antioxidant systems

• Luca Valgimigli,
• Daniele Bartolomei,
• Riccardo Amorati,
• Evan Haidasz,
• Jason J. Hanthorn,
• Susheel J. Nara,
• Johan Brinkhorst and
• Derek A. Pratt

Beilstein J. Org. Chem. 2013, 9, 2781–2792, doi:10.3762/bjoc.9.313

• antioxidants (10–12). Results and Discussion Synthesis. The preparation of compounds 4a, 4b and 5–8 involved installation of the aryl alcohol moiety as the final step via a Cu-catalyzed benzyloxylation/hydrogenolysis sequence on the corresponding pyri(mi)dyl halides, whereas the preparation of 4c, 4d and 9

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• monofluoromethylation was described by J. Hu. Aryl iodides were submitted to a Cu-catalyzed (CuTC = copper thiophene-2-carboxylate) debenzoylative fluoroalkylation with 2-PySO2CHFCOR followed by desulfonylation (Scheme 2) [49]. It has been shown that the (2-pyridyl)sulfonyl moiety is important for the Cu-catalysis. 2

• trifluoromethylations and the recent results of the Cu-catalyzed reaction described above, that of difluoromethylation has been more slowly developed. This is probably due to the lack of thermal stability of CuCHF2 [42]. To the best of our knowledge, the direct cross-coupling of CuCHF2 with aromatic halides has not

• readily available nucleophilic trifluoromethyl source after decarboxylation at high temperature in the presence of stoichiometric amounts of copper salts [78][79]. In 2011, Y. M. Li et al. showed that the Cu-catalyzed C–CF3 bond formation of iodoarenes could be achieved by using a sodium salt of

Microwave-assisted synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives through copper-catalyzed intramolecular N-arylation

• Fei Zhao,
• Lei Zhang,
• Hailong Liu,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2013, 9, 2463–2469, doi:10.3762/bjoc.9.285

• relevant examples of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives. Reagents and conditions: (a) CF3COOH, anhydrous dichloromethane, reflux; (b) NaBH4, MeOH. Optimization of the reaction conditions for the Cu-catalyzed synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline (2a).a Synthesis of 5,6-dihydroindolo

Synthesis of the spiroketal core of integramycin

• Evgeny. V. Prusov

Beilstein J. Org. Chem. 2013, 9, 2446–2450, doi:10.3762/bjoc.9.282

• PMB-protected 3-hydroxypropanal via Horner–Wadsworth-Emmons olefination, reduction to the allylic alcohol and Sharples epoxidation [8] (Scheme 2). Subsequent Cu-catalyzed epoxide-opening using methylmagnesium bromide [9] produced an inseparable mixture of 1,2- and 1,3-diol products, which upon

Cu-catalyzed trifluoromethylation of aryl iodides with trifluoromethylzinc reagent prepared in situ from trifluoromethyl iodide

• Yuzo Nakamura,
• Motohiro Fujiu,
• Tatsuya Murase,
• Yoshimitsu Itoh,
• Hiroki Serizawa,
• Kohsuke Aikawa and
• Koichi Mikami

Beilstein J. Org. Chem. 2013, 9, 2404–2409, doi:10.3762/bjoc.9.277

• ®), Bicalutamide (Casodex®), Aprepitant (Emend®), and Nilutamide (Nilandron®). Results and Discussion The preparation of the trifluoromethylzinc reagent Zn(CF3)I was initially examined in the context of the in situ Cu-catalyzed trifluoromethylation of aryl iodide 1 under various conditions. The results of the

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• reaction. Merging Au-based photoredox catalysis and Lewis base catalysis for the Mannich reaction. Merging Ru-based photoredox catalysis and Cu-catalyzed alkynylation reaction. Merging Ru-based photoredox catalysis and NHC catalysis. 1,3-Dipolar cycloaddition of photogenically formed azomethine ylides

Copper-catalyzed aerobic aliphatic C–H oxygenation with hydroperoxides

• Pei Chui Too,
• Ya Lin Tnay and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2013, 9, 1217–1225, doi:10.3762/bjoc.9.138

• Pei Chui Too Ya Lin Tnay Shunsuke Chiba Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore. Fax: +65-67911961; Tel: +65-65138013 10.3762/bjoc.9.138 Abstract We report herein Cu-catalyzed

• oxidative sp3 C–H functionalization with predictable chemo- and regioselectivity [1][2][3][4]. To achieve this goal, we have recently utilized 1,5-H-radical shift [5][6] with iminyl radical species (N-radicals) generated under Cu-catalyzed aerobic reaction conditions, in which the resulting carbon-centered

• radicals (C-radicals) could be trapped by molecular oxygen to form new C–O bonds. For instance, the Cu-catalyzed aerobic reaction of N-alkylamidines afforded aminidyl radicals (N-radicals) by single-electron oxidation and deprotonation of the amidine moiety, which was followed by 1,5-H-radical shift to

Efficient Cu-catalyzed base-free C–S coupling under conventional and microwave heating. A simple access to S-heterocycles and sulfides

• Silvia M. Soria-Castro and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2013, 9, 467–475, doi:10.3762/bjoc.9.50

• ), this Cu-catalyzed C–S coupling reaction being highly chemoselective for aryl iodides. In comparison with the already reported procedure for the preparation of S-aryl thioacetates by Pd catalysis [51][56], the methodology herein described has the advantages of using a lower-cost copper salt and a stable

• . Electron-donor and electron-acceptor substituents are tolerated, and polysubstitution can also be successfully accomplished. Experimental Representative experimental procedures for the Cu-catalyzed base-free C–S coupling Method A: The reactions were carried out in a 10 mL two-necked Schlenk tube, equipped

Tandem aldehyde–alkyne–amine coupling/cycloisomerization: A new synthesis of coumarins

• Maddi Sridhar Reddy,
• Nuligonda Thirupathi and
• Madala Haribabu

Beilstein J. Org. Chem. 2013, 9, 180–184, doi:10.3762/bjoc.9.21

• Maddi Sridhar Reddy Nuligonda Thirupathi Madala Haribabu Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow-226 001, India, Fax: +91-(522)-2623405, Tel: +91–(522)–2612 411, Extn: 4379 10.3762/bjoc.9.21 Abstract Cu-catalyzed A3 coupling of ethoxyacetylene

• biological and pharmaceutical applications. In continuation of our interest in the cycloisomerization of alkynols and alkynamines for the synthesis of various heterocycles [17][18][19][20][21][22], we herein report the synthesis of coumarins from salicylaldehydes by a Cu-catalyzed exclusive 6-endo-dig

Peptoids and polyamines going sweet: Modular synthesis of glycosylated peptoids and polyamines using click chemistry

• Daniel Fürniss,
• Timo Mack,
• Frank Hahn,
• Sidonie B. L. Vollrath,
• Katarzyna Koroniak,
• Ute Schepers and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 56–63, doi:10.3762/bjoc.9.7

• fast methods for the decoration of biomimetic molecules with sugars is of fundamental importance. The glycosylation of peptoids and polyamines as examples of such biomimetic molecules is reported here. The method uses Cu-catalyzed azide alkyne cycloaddition to promote the reaction of azidosugars with

Rh(III)-catalyzed directed C–H bond amidation of ferrocenes with isocyanates

• Satoshi Takebayashi,
• Tsubasa Shizuno,
• Takashi Otani and
• Takanori Shibata

Beilstein J. Org. Chem. 2012, 8, 1844–1848, doi:10.3762/bjoc.8.212

• reported to date, and there is only one report of enantioselective C–H activation of ferrocenes [6][7][8][9]. Schmalz et al. reported the first catalytic C–H activation of ferrocenes using a Cu-catalyzed intramolecular carbene insertion into a Cp–H bond [6]. Further, they showed that the reaction could be

Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers

• Nicola Otto and
• Till Opatz

Beilstein J. Org. Chem. 2012, 8, 1105–1111, doi:10.3762/bjoc.8.122

• tetramethylmagnolamine [6], and the antifungal diamine piperazinomycin [7] (Figure 1). A straightforward method for the formation of diaryl ethers is the Cu-catalyzed coupling of aryl halides with phenols, first reported by Fritz Ullmann in 1903 [8][9]. However, the classical protocol suffers from considerable

• Cu-catalyzed reaction in recent years [14]. It is known that certain additives, such as N,N- and N,O-chelating ligands, accelerate the Ullmann diaryl ether synthesis and permit a considerable reduction of the reaction temperature [15][16][17]. Successful approaches towards a mild coupling were, e.g

• 8-hydroxyquinoline (L47) (Table 2 and Figure 3). These ligands have been reported to be effective in the Cu-catalyzed diaryl ether synthesis before [21][27][28][29]. A disadvantage of ligands with free amino or hydroxy groups, such as L44, is that they themselves can act as substrates in the Ullmann

Synthesis of 2-amino-3-arylpropan-1-ols and 1-(2,3-diaminopropyl)-1,2,3-triazoles and evaluation of their antimalarial activity

• Matthias D’hooghe,
• Stéphanie Vandekerckhove,
• Karen Mollet,
• Karel Vervisch,
• Stijn Dekeukeleire,
• Liesbeth Lehoucq,
• Carmen Lategan,
• Peter J. Smith,
• Kelly Chibale and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2011, 7, 1745–1752, doi:10.3762/bjoc.7.205

• substrates to perform “click chemistry” [34] incorporate an azide group and an aziridine ring in their structure, for example in 2-(azidomethyl)aziridines, thus providing a direct access to 2-[(1,2,3-triazol-1-yl)methyl]aziridines through Cu-catalyzed reaction with alkynes [35]. In this work, nonactivated N

Pseudo five-component synthesis of 2,5-di(hetero)arylthiophenes via a one-pot Sonogashira–Glaser cyclization sequence

• Dominik Urselmann,
• Dragutin Antovic and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1499–1503, doi:10.3762/bjoc.7.174

• efficiency is also variable. Just recently we reported a very straightforward one-pot synthesis of symmetric 1,4-di(hetero)arylated 1,3-butadiynes starting from (hetero)aryl iodides by virtue of a sequentially Pd/Cu-catalyzed [14] Sonogashira–Glaser process (Scheme 1) [15]. According to this general one-pot

• concatenation of our sequentially Pd/Cu-catalyzed Sonogashira–Glaser reaction [15] with the sulfide-mediated cyclization should lead to a straightforward one-pot pseudo five-component synthesis of 2,5-di(hetero)arylthiophenes (Scheme 2). We first set out to identify an optimal cosolvent for all four steps

• symmetrical 2,5-di(hetero)arylthiophenes based upon an initial sequentially Pd/Cu-catalyzed Sonogashira–Glaser process followed by a subsequent sulfide-mediated cyclization. A broad range of functional groups is tolerated and the iodo substrates are either commercially available or easily accessible. This

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• completion. A variety of amines were involved in this one-pot sequential three-component reaction allowing the introduction of different protecting groups of the indole moiety. This site-selective, Pd/Cu-catalyzed cross-coupling approach was also performed on 1-chloro-2-iodo-4-(trifluoromethyl)benzene as o

Directed ortho,ortho'-dimetalation of hydrobenzoin: Rapid access to hydrobenzoin derivatives useful for asymmetric synthesis

• Inhee Cho,
• Labros Meimetis,
• Lee Belding,
• Michael J. Katz,
• Travis Dudding and
• Robert Britton

Beilstein J. Org. Chem. 2011, 7, 1315–1322, doi:10.3762/bjoc.7.154

• diiodohydrobenzoin 12 in Cu-catalyzed C–N cross-coupling reactions [33] led only to the formation of cis-4b,9b-dihydrobenzofuro[3,2-b]benzofuran (24) [34]. Consequently, the diol 12 was converted to the corresponding acetonide 25 or methyl ether 26 prior to cross-coupling. In this manner, the diphenylhydrobenzoin

Combined directed ortho-zincation and palladium-catalyzed strategies: Synthesis of 4,n-dimethoxy-substituted benzo[b]furans

• Verónica Guilarte,
• M. Pilar Castroviejo,
• Estela Álvarez and
• Roberto Sanz

Beilstein J. Org. Chem. 2011, 7, 1255–1260, doi:10.3762/bjoc.7.146

• corresponding coupled products 5–7 by using the Pd/TBAF method A, with no significant side-products (Table 2, entries 1,2,7,8 and 14). However, under these conditions bromine-containing compounds 4b,d and f afforded variable amounts of dialkynylation products in some cases, and so the Pd/Cu catalyzed procedure

Directed aromatic functionalization

• Victor Snieckus

Beilstein J. Org. Chem. 2011, 7, 1215–1218, doi:10.3762/bjoc.7.141

• exchange) chemistry, alternative and competitive combinational metal amide bases are rapidly appearing [47][48]. The first successful glimpses of the much sought after complementary, cleaner, regiodefined, and milder procedures to ortho, para versus meta SEAr reactions are being seen in Cu-catalyzed meta

One-pot four-component synthesis of pyrimidyl and pyrazolyl substituted azulenes by glyoxylation–decarbonylative alkynylation–cyclocondensation sequences

• Charlotte F. Gers,
• Julia Rosellen,
• Eugen Merkul and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1173–1181, doi:10.3762/bjoc.7.136

• novel concept combines the unique reactivity patterns of transition metal catalysis with fundamental organic reactivity, in a sequential or consecutive fashion. Over the years, we have contributed to this concept through Pd/Cu-catalyzed accesses to enones and ynones and the in situ transformation of

• , followed by Pd/Cu-catalyzed decarbonylative alkynylation with terminal alkynes 2, and finally by cyclocondensation of the ynone intermediates with substituted amidine hydrochlorides 4, pyrimidylazulenes 5 were obtained in moderate to good yields in a one-pot fashion (Scheme 5) (for experimental details

Control of asymmetric biaryl conformations with terpenol moieties: Syntheses, structures and energetics of new enantiopure C₂-symmetric diols

• Y. Alpagut,
• B. Goldfuss and
• J.-M. Neudörfl

Beilstein J. Org. Chem. 2008, 4, No. 25, doi:10.3762/bjoc.4.25

• enantioselective organozinc catalysts [14][15][16][17][18], in chiral n-butyllithium aggregates [19][20][21][22][23] and in enantioselective Pd- and Cu-catalyzed C-C-couplings [9][10][24]. Here we present syntheses and characterizations of new enantiopure C2-symmetric diols based on (−)-menthone, (−)-verbenone and

An exceptional P-H phosphonite: Biphenyl- 2,2'-bisfenchylchlorophosphite and derived ligands (BIFOPs) in enantioselective copper- catalyzed 1,4-additions

• T. Kop-Weiershausen,
• J. Lex,
• J.-M. Neudörfl and
• B. Goldfuss

Beilstein J. Org. Chem. 2005, 1, No. 6, doi:10.1186/1860-5397-1-6

• enantioslective Cu-catalyzed 1,4-additions. Results and Discussion Coupling of bis-lithiated biphenyl-2,2'-bisfenchol (BIFOL), synthesized from 2,2'-dilithiobiphenyl and (-)-fenchone, [68][69][70][71][72] with PCl3 or PBr3 yields the enantiopure halophosphites BIFOP-Cl, 1 (62% yield) and BIFOP-Br, 2 (69% yield

• ', Scheme 4). The tightest encapsulation and fenchane embedding of phosphorus atoms is apparent for the halophosphites BIFOP-Cl (1, 2.471 Å) and BIFOP-Br (2, 2.476 Å, Table 2), explaining their unusual low reactivity (Table 1). Cu-catalyzed, enantioselecitve 1,4-additions of diethylzinc to 2-cyclohexene-1

• -Et phosphonite BIFOP-Et (4) during Cu-catalyzed 1,4-additions of diethylzinc to cyclohexenone, the P-H phosphonite BIFOP-H (3) is stable and gives even a higher enantioselectivity than a corresponding phosphite or phosphoramidite. Hence, the large steric demand and the relatively low accessibility of